Methods for treating cancer with ghrh agonists

Abstract

Embodiments of the present disclosure are directed to methods to treat a subject having cancer. In one embodiment, a method of treating a subject with cancer may comprise administering a therapeutically effective amount of at least one GHRH agonist peptide in combination with at least one anticancer agent. In another embodiment, a method of killing cancer cells may comprise contacting the cancer cells with a composition comprising at least one GHRH agonist peptide and at least one anticancer agent. In some embodiments, the method may be in vitro or in vivo. In an additional embodiment, a method of killing cancer stem cells may comprise contacting the cancer stem cells with a composition comprising at least one GHRH agonist peptide and at least one anticancer agent.

What is claimed is: 
     
         1 . A method of treating a subject with cancer comprising administering a therapeutically effective amount of at least one GHRH agonist peptide in combination with at least one anticancer agent. 
     
     
         2 . The method of  claim 1 , wherein the at least one GHRH agonist peptide has the formula I:
   [R 1 -A 1 -A 2 -A 3 -Ala-Ile-A 6 -A 7 -A 8 -A 9 -A 10 -A 11 -A 12 -A 13 -A 14 -A 15 -A 16 -A 17 -A 18 -Ala-A 20 -A 21 -A 22 -A 23 -A 24 -A 25 -A 26 -A 27 -A 28 -A 29 -A 30 ]-R 2 ;   wherein,   R 1  is Ac, Tfa, alkyl, cycloalkyl, benzyl, phenyl, substituted alkyl, substituted phenyl, substituted phenyl ethyl, 2-carboxybenzamido, carboxypropyl, amino-(hydroxylphenyl)-alkyl, amino(imidazole-4-yl)-alkyl, hydroxyphenyl-alkyl, or is absent;   A 1  is Tyr, Dat, des-amino Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His, D-His, or N-Me-Tyr;   A 2  is Ala, D-Ala, Abu, D-Arg, Aib, D-N-methyl Ala, or D-Abu;   A 3  is Asp, D-Asp, Glu, or D-Glu;   A 6  is Phe, or Fpa5;   A 7  is Thr, Aib, Leu, Trp, β-Nal, or pX-Phe, where X is H, F, Cl, Br, NO 2 , or Me;   A 8  is D-Asn, Asn, Ala, Gln, Thr, N-Me-Ala, Aib, Leu, Trp, β-Nal, Ser, D-Ser, or pX-Phe, wherein X is H, F, Cl, Br, NO 2 , or Me;   A 9  is Ser, Ala, Aib, Leu, Trp, β-Nal, or pX-Phe, where X is H, F, Cl, Br, NO 2 , or Me;   A 10  is Tyr or D-Tyr;   A 11  is Arg, His, Gap, Gab, or Har;   A 12  is Orn, Arg, Lys, D-Lys, Lys(Me) 2 , Gap, Gab, N-alkyl-Lys, or N-cycloalkyl-Lys;   A 13  is Val or Ile;   A 14  is Leu or D-Leu;   A 15  is Abu, Gly, Leu, Asn, Gln, Aib, D-Ala, or Ala;   A 16  is Gln, Ala, or Aib;   A 17  is Leu or D-Leu;   A 18  is Ser or Tyr;   A 20  is Arg, His, Gap, Gab, or Har;   A 21  is Orn, Lys, D-Lys, Arg, D-Arg, Gap, Gab, or Lys(Me) 2 ;   A 22  is Leu, Ala, Abu, Lys, or Orn;   A 23  is Leu, D-Leu, Ala, or Abu;   A 24  is Gln, His, Ala, or Aib;   A 25  is Asp, Glu, D-Glu, D-Asp, Ala, or Aib;   A 26  is Ile or Leu;   A 27  is Nle, Met, D-Met, Ala, Ile, Leu, Nva, or Val;   A 28  is Ser, Asn, or Asp;   A 29  is Arg, Har, Agm, D-Arg, D-Har, or D-Har;   A 30  is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent; and   R 2  is —NH 2 , —NH—CH 3 , —NH—CH 2 —CH 3 , —OH, —CH 2 ) p —NH—C(NH 2 )═NH, —NH(CH 2 ) p —C(═O)—NH 2 , —NHR 3 , —N(R 3 ) 2 , or —OR 3 , where p is an integer from 1 to 15, and R 3  is any of C 1-12  alkyl, C 2-12  alkenyl, or C 2-12  alkynyl, and pharmaceutically acceptable salts thereof, and   wherein the agonist peptide is different from SEQ ID NO: 1 in at least one amino acid residue.   
     
     
         3 . The method of  claim 1 , wherein the at least one GHRH agonist peptide has the formula II:
   [R 1 -A 1 -A 2 -Asp-Ala-Ile-A 6 -Thr-A 8 -Ser-Tyr-A 11 -A 12 -Val-Leu-A 15 -Gln-Leu-Ser-Ala-A 20 -A 21 -A 22 -Leu-Gln-Asp-Ala-Ile-Nle 27 -A 28 -A 29 -A 30 ]-R 2 ,   wherein   R 1  is Ac, Tfa, or is absent,   A 1  is Tyr, Dat, or N-Me-Tyr,   A 2  is Ala, D-Ala, Abu, or D-Abu,   A 6  is Phe or Fpa5,   A 8  is Asn, Ala, Gln, Thr, or N-Me-Ala,   A 11  is Arg, His, or Har,   A 12  is Orn, or Lys(Me) 2 ,   A 15  is Abu or Ala,   A 20  is Arg, His, or Har,   A 21  is Orn, or Lys(Me) 2 ,   A 22  is Leu, or Orn,   A 28  is Ser, or Asp,   A 29  is Arg, Har, Agm, D-Arg, or D-Har,   A 30  is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,   R 2  is —NH 2 , —NH—CH 3 , NH—CH 2 —CH 3 , —NH—CH 3 , —OH, —NHR 3 , —N(R 3 ) 2 , or —OR 3 , wherein R 3  is any of C 1-12  alkyl, C 2-12  alkenyl, or C 2-12  alkynyl,   and pharmaceutically acceptable salts thereof, and wherein the agonist peptide is different from SEQ ID NO: 1 in at least one amino acid residue.   
     
     
         4 . The method of  claim 1 , wherein the at least one GHRH agonist peptide is of formula III: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 1 , wherein the at least one GHRH agonist peptide is of formula IV:
   Z 1 -Z 2 -Asp-Ala-Ile-Phe-The-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Z 3 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Z 4 -Z 5 -Arg-Gln-Gln-Gly-Glu-Z 6 -Asn-Gln-Glu-Z-Gly-Ala-OH,  (IV)
   wherein   Z 1  is a D- or L-isomer of the aminoacid tyrosine or histidine;   Z 2  is a D- or L-isomer of the aminoacid alanine, valine, or isoleucine;   Z 3  is a D- or L-isomer of the aminoacid alanine or glycine;   Z 4  is a D- or L-isomer of the aminoacid methionine or leucine;   Z 5  is a D- or L-isomer of the aminoacid serine or asparagine;   Z 6  is a D- or L-isomer of the aminoacid arginine or serine; and   Z 7  is a D- or L-isomer of the aminoacid glutamine or arginine.   
     
     
         6 . The method of  claim 1 , wherein the at least one GHRH agonist peptide is a stapled GHRH agonist peptide of formula V. 
     
     
         7 . The method of  claim 1 , wherein the at least one GHRH agonist peptide is tesamorelin. 
     
     
         8 . The method of  claim 1 , wherein the at least one GHRH peptide is selected from GHRH (1-30) represented by SEQ ID NO: 1, GHRH(1-44) represented by SEQ ID NO: 43, AKL-0707, and any combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the cancer is selected from colorectal cancer, breast cancer, ovarian cancer, pancreatic cancer, head and neck cancer, bladder cancer, liver cancer, renal cancer, melanoma, gastrointestinal cancer, prostate cancer, small cell and non-small cell lung cancer, sarcomas, glioblastoma, T- and B-cell lymphoma, endometrial cancer, and cervical cancer. 
     
     
         10 . The method of  claim 1 , wherein the administration of the at least one GHRH agonist peptide is by parenteral administration selected from the group consisting of subcutaneous, intramuscular, intraperitoneal, intracavity, intrathecal, transdermal and intravenous injection. 
     
     
         11 . The method of  claim 1 , wherein the GHRH agonist peptide is selected from:
 P-20103 [N-Me-Tyr 1 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 (SEQ ID NO: 2);   P-20105 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 ;   P-20107 [N-Me-Tyr 1 , Fpa5 6 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 (SEQ ID NO: 3);   P-20109 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 ;   P-20110 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Agm 29 ]hGHRH(1-29) NH 2 ;   P-20111 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 ,Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 ;   P-20113 [N-Me-Tyr 1 , Fpa5 6 , Orn 21 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29) NH 2 (SEQ ID NO: 4);   P-20115 [N-Me-Tyr 1 , Fpa5 6 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29)NH 2 (SEQ ID NO: 5);   P-20117 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Agm 29 ]hGHRH (1-29) NH 2 ;   P-20350 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29) NH 2 ;   P-20351 [Ac-N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 ;   P-20356 [N-Me-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29) NH 2  (SEQ ID NO: 6);   P-20357 [Dat 1 , D-Ala 2 , N-Me-Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29)NH 2 ;   P-20358 [N-Me-Tyr 1 , D-Ala 2 , N-Me-Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 ;   P-20359 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29)NH 2 ;   P-20360 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29)NH 2 ;   P-20361 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29)NH 2 ;   P-20367 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29)NH 2 ;   P-20370 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 7);   P-20371 [N-Me-Tyr 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29) NH 2  (SEQ ID NO: 8);   P-20372 [N-Me-Tyr 1 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29) NH 2  (SEQ ID NO: 9);   P-20373 [N-Me-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 10);   P-20374 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Agm 29 ]hGHRH(1-29) NH 2  (SEQ ID NO: 11);   P-20375 [N-Me-Tyr 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 12);   P-20376 [N-Me-Tyr 1 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 13);   P-21300 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21301 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 14);   P-21303 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21304 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21305 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21306 [Dat 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21307 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21308 [Dat 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21309 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Ala 8 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21310 [Dat 1 -D-Ala 2 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21311 [N-Me-Tyr 1 , D-Ala 2 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-22325 [N-Me-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH (1-30)NH 2  (SEQ ID NO: 15);   P-22326 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2 ;   P-22327 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 16);   P-22328 [Ac-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2 ;   P-22329 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Apa 30 ]hGHRH(1-30)NH 2 ;   P-22330 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2 ;   P-22331 [N-Me-Tyr 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2 ;   P-22332 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 17);   P-22334 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Apa 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 18);   P-22335 [N-Me-Tyr 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 19);   P-22336 [N-Me-Tyr 1  Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 20);   P-22337 [N-Me-Tyr 1 , D-Ala 2 , Cpa 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2 ;   P-23250 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23251 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 21);   P-23252 [Dat 1 -D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23253 [Dat 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 22);   P-23254 [Dat 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23255 [Dat 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 23);   P-23256 [Dat 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23257 [Dat 1 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 24);   P-23258 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23259 [N-Me-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 (SEQ ID NO: 25);   P-23260 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23261 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 26);   P-23262 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23263 [N-Me-Tyr 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 27);   P-23264 [N-Me-Tyr 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23265 [N-Me-Tyr 1 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 28);   P-24340 [N-Me-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 29);   P-24341 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2 ;   P-24342 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 30);   P-24344 [Dat 1 -D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2 ;   P-24345 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2 ;   P-24346 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Aha 30 ]hGHRH (1-30)NH 2 ;   P-24347 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2 ;   P-24348 [N-Me-Tyr 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2 ;   P-25501 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH 2 ;   P-25502 [Dat 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH 2 ;   P-25503 [N-Me-Tyr 1 , Abu 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 31);   P-25504 [Dat 1 , D-Abu 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH 2 ;   P-25506 [N-Me-Tyr 1 , D-Abu 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30) NH 2 ;   P-25508 [Tfa-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH 2 ;   P-25516 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Gab 30 ]hGHRH(1-30)NH 2 ;   P-26802 [Dat 1 , D-Ala 2 , Thr 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Ada 30 ]hGHRH(1-30)NH 2 ;   P-26803 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Ada 30 ]hGHRH(1-30)NH—CH 3 ;   P-26804 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Ada 30 ]hGHRH(1-30)NH 2 ;   P-27400 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3 ;   P-27401 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27403 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3 ;   P-27404 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH (1-29)NH—CH 3 ;   P-27405 [N-Me-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 3  (SEQ ID NO: 32);   P-27406 [N-Me-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29) NH—CH 3  (SEQ ID NO: 33);   P-27407 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3  (SEQ ID NO: 34);   P-27408 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-30)NH—CH 3 ;   P-27409 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3 ;   P-27410 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGH RH(1-29)NH—CH 3 ;   P-27411 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29) NH—CH 3 ;   P-27412 [N-Me-Tyr 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH (1-29)NH—CH 3 ;   P-27413 [Dat 1 , Gln 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 ]hGHRH (1-29)NH—CH 3 (SEQ ID NO: 35);   P-27414 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH—CH 3 ;   P-27415 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH—CH 3  (SEQ ID NO: 36);   P-27416 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3 ;   P-27417 [Ac-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29) NH—CH 3 ;   P-27418 [Ac-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3 ;   P-27419 [Ac-Tyr 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 3  (SEQ ID NO: 37);   P-27422 [N-Me-D-Tyr 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29) NH—CH 3 ;   P-27423 [N-Me-D-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 2 ]hGHRH(1-29)NH—CH 3 ;   P-27424 [Dat 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 3  (SEQ ID NO: 38);   P-27425 [N-Me-D-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3 ;   P-27440 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27441 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27442 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27443 [N-Me-Tyr 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27444 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27445 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27446 [N-Me-Tyr 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27447 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH—CH 3 ;   P-27448 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH—CH 3 ;   P-27449 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH—CH 3 ;   P-27450 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH—CH 3 ;   P-27451 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH—CH 3 ;   P-28420 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28421 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29) NH—CH 2 —CH 3 ;   P-28430 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29) NH—CH 2 —CH 3 ;   P-28431 [N-Me-Tyr 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28460 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28461 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29) NH—CH 2 —CH 3 ;   P-28462 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29) NH—CH 2 —CH 3 ;   P-28463 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28464 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH (1-29)NH—CH 2 —CH 3 ;   P-28465 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28466 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH (1-29)NH—CH 2 —CH 3 ;   P-28467 [N-Me-Tyr 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29) NH—CH 2 —CH 3 ;   P-28468 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28469 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28470 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28471 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28472 [Dat 1 , D-Ala 2 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28473 [Dat 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28474 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28475 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH—CH 2 —CH 3 ;   P-28476 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH—CH 2 —CH 3 ;   P-28477 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH—CH 2 —CH 3 ;   P-28478 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH—CH 2 —CH 3 ;   P-28479 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH—CH 2 —CH 3 ;   P-29701 [N-Me-Tyr 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Gln-Gab 30 ]hGHRH](1-30)NH 2 ;   P-29702 [Dat 1 , D-Ala 2 , Orn 12 , Abu 11 , Orn 21 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29703 [N-Me-Tyr 1 ,Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 39);   P-29704 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21,22 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29706 [Tfa-Tyr 1 , D-Abu 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29708 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29710 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29720 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29721 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 2122 , Nle 27 , Asp 28 , Gln-Gab 30 ]hGHRH(1-30) NH 2 ;   P-29722 [Tfa-Tyr 1 , D-Abu 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Gln 30 , Gab 31 ]hGHRH(1-30)NH 2 ;   P-29723 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Gln-Gab 30 ]hGHRH (1-30)NH 2 ;   P-29724 [N-Me-Tyr 1 , D-Ala 2 , Fpa5 6 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Gln Gab 30 ]hGHRH(1-30)NH 2 ;   JI-34 [Dat 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 40);   JI-36 [Dat 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 41); and   JI-38 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 42).   
     
     
         12 . The method of  claim 1 , wherein the GHRH agonist is selected from:
 P-20350 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29) NH 2 ;   P-20357 [Dat 1 , D-Ala 2 , N-Me-Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH (1-29)NH 2 ;   P-21300 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21304 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21306 [Dat 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21308 [Dat 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-21310 [Dat 1 -D-Ala 2 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 , Amc 30 ]hGHRH(1-30)NH 2 ;   P-22327 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Apa 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 16);   P-23250 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23251 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 21);   P-23252 [Dat 1 -D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23253 [Dat 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 22);   P-23254 [Dat 1 , D-Ala 2 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23255 [Dat 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 23);   P-23256 [Dat 1 , D-Ala 2 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2 ;   P-23257 [Dat 1 , Ala 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Har 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 24);   P-24342 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2  (SEQ ID NO: 30);   P-24344 [Dat 1 -D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Aha 30 ]hGHRH(1-30)NH 2 ;   P-25502 [Dat 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH 2 ;   P-25504 [Dat 1 , D-Abu 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gab 30 ]hGHRH(1-30)NH 2 ;   P-26802 [Dat 1 , D-Ala 2 , Thr 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Ada 30 ]hGHRH(1-30)NH 2 ;   P-27400 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3 ;   P-27401 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-27407 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 3  (SEQ ID NO: 34);   P-27408 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-30)NH—CH 3 ;   P-27413 [Dat 1 , Gln 8 , His 11 , Orn 12 , Abu 15 , His 20 , Orn 21 , Nle 27 , Asp 28 ]hGHRH (1-29)NH—CH 3  (SEQ ID NO: 35);   P-27424 [Dat 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 3  (SEQ ID NO: 38);   P-27440 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , D-Arg 29 ]hGHRH(1-29)NH—CH 3 ;   P-28469 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28470 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28471 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28472 [Dat 1 , D-Ala 2 , Fpa5 6 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28473 [Dat 1 , D-Ala 2 , Fpa5 6 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-28474 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 ]hGHRH(1-29)NH—CH 2 —CH 3 ;   P-29702 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29704 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 21,22 , Nle 27 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29720 [Dat 1 , D-Ala 2 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Gln-Gab 30 ]hGHRH(1-30)NH 2 ;   P-29721 [Dat 1 , D-Ala 2 , Gln 8 , Orn 12 , Abu 15 , Orn 2122 , Nle 27 , Asp 28 , Gln-Gab 30 ]hGHRH(1-30) NH 2 ;   JI-34 [Dat 1 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 40);   JI-36 [Dat 1 , Thr 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2  (SEQ ID NO: 41); and   JI-38 [Dat 1 , Gln 8 , Orn 12 , Abu 15 , Orn 21 , Nle 27 , Asp 28 , Agm 29 ]hGHRH(1-29)NH 2 (SEQ ID NO: 42).   
     
     
         13 . The method of  claim 1 , further comprising administering the GHRH agonist peptide to the subject before the cancer treatment, concurrently with the cancer treatment, post-treatment, or during remission of the cancer. 
     
     
         14 . The method of  claim 1 , wherein the at least one anticancer agent is selected from tamoxifen, toremifen, raloxifene, droloxifene, iodoxyfene, megestrol acetate, anasfrozole, letrazole, borazole, exemestane, flutamide, nilutamide, bicalutamide, cyproterone acetate, goserelin acetate, luprolide, finasteride, herceptin, methotrexate, 5-fluorouracil, cytosine arabinoside, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin, mithramycin, cisplatin, carboplatin, melphalan, chlorambucil, busulphan, cyclophosphamide, ifosfamide, nitrosoureas, thiotephan, vincristine, taxol, taxotere, etoposide, teniposide, amsacrine, Irinotecan, topotecan, epothilones, gefitinib, erlotinib, angiogenesis inhibitors, EGF inhibitors, VEGF inhibitors, CDK inhibitors, cytokines, Her1 and Her2 inhibitors, and monoclonal antibodies. 
     
     
         15 . The method of  claim 1 , wherein the at least one GHRH agonist peptide is co-administered, concurrently administered, or sequentially administered with at least one anticancer agent. 
     
     
         16 . The method of  claim 1 , wherein the GHRH agonist peptide is JI-34 and the anticancer agent is doxorubicin. 
     
     
         17 . A method of killing cancer cells, the method comprising contacting the cancer cells with a composition comprising at least one GHRH agonist peptide and at least one anticancer agent. 
     
     
         18 . The method of  claim 17 , wherein the at least one GHRH agonist peptide has the formula II:
   [R 1 -A 1 -A 2 -Asp-Ala-Ile-A 6 -Thr-A 8 -Ser-Tyr-A 11 -A 12 -Val-Leu-A 15 -Gln-Leu-Ser-Ala-A 20 -A 21 -A 22 -Leu-Gln-Asp-Ile-Nle 27 -A 28 -A 29 -A 30 ]-R 2 ,   wherein   R 1  is Ac, Tfa, or is absent,   A 1  is Tyr, Dat, or N-Me-Tyr,   A 2  is Ala, D-Ala, Abu, or D-Abu,   A 6  is Phe or Fpa5,   A 8  is Asn, Ala, Gln, Thr, or N-Me-Ala,   A 11  is Arg, His, or Har,   A 12  is Orn, or Lys(Me) 2 ,   A 15  is Abu or Ala,   A 20  is Arg, His, or Har,   A 21  is Orn, or Lys(Me) 2 ,   A 22  is Leu, or Orn,   A 28  is Ser, or Asp,   A 29  is Arg, Har, Agm, D-Arg, or D-Har,   A 30  is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,   R 2  is —NH 2 , —NH—CH 3 , NH—CH 2 —CH 3 , —NH—CH 3 , —OH, —NHR 3 , —N(R 3 ) 2 , or —OR 3 , wherein R 3  is any of C 1-12  alkyl, C 2-12  alkenyl, or C 2-12  alkynyl,   and pharmaceutically acceptable salts thereof, and wherein the GHRH agonist peptide is different from SEQ ID NO: 1 in at least one amino acid residue.   
     
     
         19 . The method of  claim 17 , wherein the cancer cell is selected from a colorectal cancer cell, a breast cancer cell, an ovarian cancer cell, a pancreatic cancer cell, a head and neck cancer cell, a bladder cancer cell, a liver cancer cell, a renal cancer cell, a melanoma cell, a gastrointestinal cancer cell, a prostate cancer cell, a small cell lung cancer cell, non-small cell lung cancer cell, a sarcoma cell, a glioblastoma cell, T- and B-cell lymphoma cell, a endometrial cancer cell, and a cervical cancer cell. 
     
     
         20 . A method of killing cancer stem cells, the method comprising contacting the cancer stem cells with a composition comprising at least one GHRH agonist peptide and at least one anticancer agent. 
     
     
         21 . The method of  claim 20 , wherein the at least one GHRH agonist peptide has the formula II:
   [R 1 -A 1 -A 2 -Asp-Ala-Ile-A 6 -Thr-A 8 -Ser-Tyr-A 11 -A 12 -Val-Leu-A 15 -Gln-Leu-Ser-Ala-A 20 -A 21 -A 22 -Leu-Gln-Asp-Ile-Nle 27 -A 28 -A 29 -A 30 ]-R 2 ,   wherein   R 1  is Ac, Tfa, or is absent,   A 1  is Tyr, Dat, or N-Me-Tyr,   A 2  is Ala, D-Ala, Abu, or D-Abu,   A 6  is Phe or Fpa5,   A 8  is Asn, Ala, Gln, Thr, or N-Me-Ala,   A 11  is Arg, His, or Har,   A 12  is Orn, or Lys(Me) 2 ,   A 15  is Abu or Ala,   A 20  is Arg, His, or Har,   A 21  is Orn, or Lys(Me) 2 ,   A 22  is Leu, or Orn,   A 28  is Ser, or Asp,   A 29  is Arg, Har, Agm, D-Arg, or D-Har,   A 30  is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,   R 2  is —NH 2 , —NH—CH 3 , NH—CH 2 —CH 3 , —NH—CH 3 , —OH, —NHR 3 , —N(R 3 ) 2 , or —OR 3 , wherein R 3  is any of C 1-12  alkyl, C 2-12  alkenyl, or C 2-12  alkynyl,   and pharmaceutically acceptable salts thereof, and wherein the GHRH agonist peptide is different from SEQ ID NO: 1 in at least one amino acid residue.   
     
     
         22 . The method of  claim 20 , wherein the at least one anticancer agent is selected from tamoxifen, toremifen, raloxifene, droloxifene, iodoxyfene, megestrol acetate, anasfrozole, letrazole, borazole, exemestane, flutamide, nilutamide, bicalutamide, cyproterone acetate, goserelin acetate, luprolide, finasteride, herceptin, methotrexate, 5-fluorouracil, cytosine arabinoside, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin, mithramycin, cisplatin, carboplatin, melphalan, chlorambucil, busulphan, cyclophosphamide, ifosfamide, nitrosoureas, thiotephan, vincristine, taxol, taxotere, etoposide, teniposide, amsacrine, Irinotecan, topotecan, epothilones, gefitinib, erlotinib, angiogenesis inhibitors, EGF inhibitors, VEGF inhibitors, CDK inhibitors, cytokines, Her1 and Her2 inhibitors, and monoclonal antibodies.